Potential radiosensitizing agents. Dinitroimidazoles.

  title={Potential radiosensitizing agents. Dinitroimidazoles.},
  author={K. Agrawal and K. Bears and R. K. Sehgal and J. N. Brown and P. E. Rist and W. Rupp},
  journal={Journal of medicinal chemistry},
  volume={22 5},
New compounds of the nitroimidazole series have been synthesized as radiosensitizers which selectively sensitize hypoxic cells to the lethal effect of radiation. The reaction of 2,4(5)-dinitroimidazole (2) with chloroethanol or hydrochloric acid yielded 4(5)-nitro-5(4)-chloroimidazole (3), which upon reaction with ethylene oxide yielded the 4-nitro-5-chloroimidazole-1-ethanol (6). Reaction of 2 with ethylene oxide resulted in a mixture of two compounds, the 2,4-dinitroimidazole-1-ethanol (4… Expand
Radiosensitization of hypoxic mammalian cells by dinitroimidazoles.
2,4-dinitroimidazole-t-ethanol (KA161) was the most effective radiosensitizer producing an enhancement ratio of 2.0 at 100 ..mu..m concentration and was found to be more efficient than misonidazoles at this concentration. Expand
Potential Radiosensitizing Agents III: 2-Nitro-4-acetylimidazole analogs.
New analogs of 2-nitroimidazole have been synthesized in an effort to minimize the toxicity and increase selective sensitization of hypoxic mammalian cells toward lethal effects of ionizing radiation suggesting that the 3-methoxy-2-propanol analog may possess a therapeutic advantage over misonidazoles. Expand
Radiation sensitization and chemical studies on isoindole-4,7-diones.
The mechanisms of action of these new radiosensitizers are comparable to those of other electron-affinic sensitizers, and it is anticipated that the compounds studied will provide a basis for the development of a new class of radiosensitized chemicals. Expand
The Chemistry of Nitroimidazole Hypoxic Cell Radiosensitizers
It is now well recognised that the imidazole ring system is an important component of many different types of natural products having a wide range of biological activities, including those essentialExpand
Development of radiosensitizers: a medicinal chemistry perspective.
The objective of this chapter is to critically review electron affinic radiosensitizers from the medicinal chemist's perspective with the goal of discovering new clinically useful radiosensitized cells. Expand
Micellar Effects on the Radiation Chemistry of Biologically Important Compounds
Micellar effects on the steady state and pulse radiolytic studies of different biologically important compounds such as purine bases, Vitamin K, Folic acid, and radiosensitizers isoindole quinonesExpand
N-Trinitroethylamino functionalization of nitroimidazoles: a new strategy for high performance energetic materials
An N-functionalized strategy, including N-amination and N-trinitroethylamination, was utilized for the synthesis of nitroimidazole-based energetic materials, giving rise to a new family of highlyExpand
Synthesis and in vitro evaluation of new 5-substituted 6-nitroimidazooxazoles as antikinetoplastid agents.
The synthesis of new 5-substituted 6-nitroimidazooxazole derivatives showed more promising results, particularly against T. cruzi, with IC50 > 10 μM, while the second series of compounds bearing an ethynyl aryl substituent in 5-position showed more promise. Expand
An efficient radiosynthesis of [18F]fluoromisonidazole.
  • J. L. Lim, M. Berridge
  • Chemistry, Medicine
  • Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
  • 1993
An efficient preparation of the hypoxic cell tracer [ 18F]3-fluoro-1-(2'-nitro-1'-imidazolyl)-2-propanol ([18F]fluoromisonidazole) is reported, which is of interest to probe hypoxic tissue in infarcts and tumors. Expand
Effect of hypoxic cell radiosensitizers on glutathione level and related enzyme activities in isolated rat hepatocytes.
Addition of partially purified glutathione S-transferase (GST) did not enhance DNIE-mediated GSH loss in a cell-free system, while misonidazole and KIH-3 did not. Expand